Long non-coding RNAs (lncRNAs) have been found essential for tumorigenesis of prostate cancer (PC), but its role in the regulation of castration-resistant prostate cancer (CRPC) is poorly identified. Here, we showed that a lncRNA, Breast-Cancer Anti-Estrogen Resistance 4 (BCAR4), which plays a pivotal role in the tamoxifen-resistance of breast cancer, was significantly upregulated in CRPC, but not in castration-sensitive prostate cancer (CSPC), compared to normal prostate tissue. High BCAR4 levels in CRPC were correlated with poor patients' overall survival. Androgen increased growth and migration of androgen receptor (AR)-positive PC346 cells, which was abolished by the antagonist of androgen. Overexpression of BCAR4 in PC346 cells increased cell growth and migration, but turned the cells insensitive to androgen. On the other hand, growth and migration of AR-negative DU145 cells are insensitive to androgen, while depletion of BCAR4 in DU145 cells not only decreased cell growth, but also turned the cells sensitive again to androgen. Moreover, BCAR4 activated GLI2 downstream genes, and correlated with the levels of these GLI2-target genes in CRPC. Depletion of GLI2 abolished the effects of BCAR4 on cell growth and migration. Together, our data suggest that BCAR4 may activate GLI2 signaling in PC to contribute to castration resistance.
Aging. 2018 Dec 04 [Epub ahead of print]
Zhiping Cai, Yapei Wu, Yao Li, Jizhong Ren, Linhui Wang
Department of Urology, Shanghai Changzheng Hospital, Shanghai 200003, China., Department of Urology, Huashan Hospital, Shanghai 200010, China.